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AR062526A1 - DERIVADOS DE 4-(3-METILMORFOLIN-4-IL)PIRIMIDINA Y MORFOLIN-4-IL-PIRIMIDINA COMO INHIBIDORES DE MTOR QUINASA Y PI3K, UNA COMPOSICIoN FARMACEUTICA QUE LOS COMPRENDE Y EL USO DE LOS MISMOS EN LA FABRICACION DE MEDICAMENTOS PARA EL TRATAMIENTO DE DIVERSOS TIPOS DE CANCER. - Google Patents

DERIVADOS DE 4-(3-METILMORFOLIN-4-IL)PIRIMIDINA Y MORFOLIN-4-IL-PIRIMIDINA COMO INHIBIDORES DE MTOR QUINASA Y PI3K, UNA COMPOSICIoN FARMACEUTICA QUE LOS COMPRENDE Y EL USO DE LOS MISMOS EN LA FABRICACION DE MEDICAMENTOS PARA EL TRATAMIENTO DE DIVERSOS TIPOS DE CANCER.

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Publication number
AR062526A1
AR062526A1 ARP070103775A ARP070103775A AR062526A1 AR 062526 A1 AR062526 A1 AR 062526A1 AR P070103775 A ARP070103775 A AR P070103775A AR P070103775 A ARP070103775 A AR P070103775A AR 062526 A1 AR062526 A1 AR 062526A1
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AR
Argentina
Prior art keywords
alkyl
6alkyl
alkoxy
aminoc1
haloc1
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ARP070103775A
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English (en)
Inventor
Heather Finlay
Kurt Gordon Pike
Jeffrey Morris
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Astrazeneca Ab
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Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38720451&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR062526(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GB0616747A external-priority patent/GB0616747D0/en
Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of AR062526A1 publication Critical patent/AR062526A1/es

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    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Un compuesto de formula (1) o una sal aceptable para uso farmacéutico del mismo, composiciones farmacéuticas que los comprenden y el uso do los mismos en terapia, por ejemplo, en el tratamiento de enfermedades proliferativas, tal como cáncer y, en particular, en enfermedades mediadas por una mTOR quinasa y/o uno o más enzimas PI3K. Reivindicacion 1: Un compuesto, caracterizado porque es de formula (1) o una sal aceptable para uso farmacéutico del mismo; donde m es 0, 1, 2, 3 o 4; Y1 e Y2 son independientemente N o CR8, con la condicion de que uno sea N y el otro sea CR8; X es un grupo ligador seleccionado entre -CR4=CR5-, -CR4=CR5CR6R7-, -CR6R7CR5=CR4-, -C:::C-, -C:::CCR6R7.-, -CR6R7C:::C-, -NR4CR6R7-, -OCR6R7-, - SCR6R7-, - S(O)CR6R7-, -S(O)2CR6R7-, -C(O)NR4CR6R7-, -NR4C(O)CR6R7-, -NR4C(O)NR5CR6R7-, -NR4S(O)2CR6R7-, -S(O)2NR4CR6R7-, -C(O)NR4-, - NR4C(O)-, -NR4C(O)NR5-, -S(O)2NR4- y -NR4S(O)2-; R1 es un grupo seleccionado entre hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, carbociclil C1-6alquilo, heterociclilo y heterociclil C1-6alquilo, donde dicho grupo se encuentra opcionalmente sustituido con uno o más grupos seleccionados entre halo, ciano, nitro, R9, -OR9, -SR9, -SOR9, -SO2R9, - COR9, -CO2R9, -CONR9R10, -NR9R10, -NR9COR10, -NR9CO2R10, -NR9CONR10R15, -NR9COCONR10R15 y -NR9SO2R10; R2 es un grupo seleccionado entre alquilo C1-6, carbociclilo y heterociclilo, donde dicho grupo se encuentra sustituido con -NR17CONR18R19 y, opcionalmente, con uno o más grupos seleccionados independientemente entre halo, ciano, nitro, -R11, -OR11, -SR11, -SOR11, -SO2R11, -COR11, -CO2R11, -CONR11R12, -NR11R12, -NR11COR12, y -NR11COCONR12R16; cada R3, cuando está presente, es seleccionado independientemente entre halo, ciano, nitro, -R13, -OR13, -SR13, -SOR13 -SO2R13, -COR13, -CO2R13, -CONR13R14, -NR13R14, -NR13COR14, -NR13CO2R14 y -NR13SO2R14; R4 y R5 son independientemente hidrogeno o alquilo C1-6; o R1 y R4, junto con el átomo o átomos al cual están unidos, forman un anillo carbociclilo o heterociclilo de 4 a 10 miembros, donde 1, 2 o 3 átomos de carbono del anillo son opcionalmente reemplazados por N, O o S y donde dicho anillo se encuentra opcionalmente sustituido con uno o más grupos seleccionados entre halo, ciano, nitro, hidroxi, oxo, alquilo C1-6, alcoxilo C1-6, haloC1-6alquilo, haloC1-6alcoxilo, hidroxiC1-6alquilo, hidroxiC1-6alcoxilo, alcoxi C1-6-alquilo C1-6, alcoxi C1-6-alcoxilo C1-6, amino, alquilamino C1-6, bi(alquil C1-6)amino, aminoC1-6alquilo, alquil C1-6-aminoC1-6alquilo, bi(alquil C1-6)aminoC1-6alquilo, cianoC1-6alquilo, alquilsulfonilo C1-6, alquilsulfonilamino C1-6, alquilsulfonil C1-6-alquilC1-6amino, sulfamoilo, alquilsulfamoilo C1-6, bi(alquil C1-6)sulfamoilo, alcanoilamino C1-6, alcanoil C1-6-alquil C1-6amino, carbamoilo, alquilcarbamoilo C1-6 y bi(alquil C1-6)carbamoilo; R6 y R7 se seleccionan independientemente entre hidrogeno, halo, ciano, nitro y alquilo C1-6; R8 se selecciona entre hidrogeno, halo, ciano y alquilo C1-6; R9 y R10 son independientemente hidrogeno o un grupo seleccionado entre alquilo C1-6, carbociclilo, carbociclilC1-6alquilo, heterociclilo y heterociclilC1-6alquilo, donde dicho grupo se encuentra opcionalmente sustituido con uno o más grupos seleccionados entre halo, ciano, nitro, hidroxi, alquilo C1-6, alcoxilo C1-6, haloC1-6alquilo, haloC1-6alcoxilo, hidroxiC1-6alquilo, hidroxiC1-6alcoxilo, alcoxi C1-6-alquilo C1-6, alcoxi C1-6- alcoxilo C1-6, amino, alquilamino C1-6, bi(alquil C1-6)amino, aminoC1-6alquilo, alquil C1-6-aminoC1-6alquilo, bi(alquil C1-6)aminoC1-6alquilo, cianoC1-6alquilo, alquilsulfonilo C1-6, alquilsulfonilamino C1-6, alquilsulfonil C1-6-alquilC1-6amino, sulfamoilo, alquilsulfamoilo C1-6, bi(alquil C1-6)sulfamoilo, alcanoilamino C1-6, alcanoil C1-6-alquilC1-6amino, carbamoilo, alquilcarbamoilo C1-6 y bi(alquil C1-6)carbamoilo; R11, R12, R17 y R18 son independientemente hidrogeno o un grupo seleccionado entre alquilo C1-6, carbociclilo, carbociclilC1-6alquilo, heterociclilo y heterociclilC1-6alquilo, donde dicho grupo se encuentra opcionalmente sustituido con uno o más grupos seleccionados entre halo, ciano, nitro, hidroxi, alquilo C1- 6, alcoxilo C1-6, haloC1-6alquilo, haloC1-6alcoxilo, hidroxiC1-6alquilo, hidroxiC1-6alcoxilo, alcoxi C1-6-alquilo C1-6, alcoxi C1-6-alcoxilo C1-6, amino, alquilamino C1-6, bi(alquil C1-6)amino, aminoC1-6alquilo, alquil C1-6-aminoC1-6alquilo, bi(alquil C1-6)aminoC1-6alquilo, cianoC1-6alquilo, alquilsulfonilo C1-6, alcanoilamino C1-6, alcanoil C1-6-alquil C1-6amino, carbamoilo, alquilcarbamoilo C1-6 y bi(alquil C1-6)carbamoilo; R13, R14, R15, R16 y R19 son independientemente hidrogeno o un grupo seleccionado entre alquilo C1-6, carbociclilo, carbociclilC1-6alquilo, heterociclilo y heterociclilC1-6alquilo, donde dicho grupo se encuentra opcionalmente sustituido con uno o más grupos seleccionados entre halo, ciano, nitro, hidroxi, alquilo C1-6, alcoxilo C1-6, haloC1-6alquilo, haloC1-6alcoxilo, hidroxiC1-6alquilo, hidroxiC1-6alcoxilo, alcoxi C1-6-alquilo C1-6, alcoxi C1-6-alcoxilo C1-6, amino, alquilamino C1-6, bi(alquil C1-6)amino, aminoC1-6alquilo, alquil C1-6-aminoC1- 6alquilo, bi(alquil C1-6)aminoC1-6alquilo, cianoC1-6alquilo, alquilsulfonilo C1-6, alquilsulfonilamino C1-6, alquilsulfonil C1-6-alquilC1-6amino, sulfamoilo, alquilsulfamoilo C1-6, bi(alquil C1-6)sulfamoilo, alcanoilamino C1-6, alcanoil C1-6-alquil C1-6amino, carbamoilo, alquilcarbamoilo C1-6 y bi(alquil C1-6)carbamoilo; o R18 y R19 forman, junto con el átomo de nitrogeno al cual se encuentran unidos, un anillo heterociclilo de 3 a 10 miembros, donde 1 o 2 átomos de carbono del anillo son opcionalmente reemplazados por N, O o S y donde dicho anillo se encuentra opcionalmente sustituido con uno o más grupos seleccionados entre halo, ciano, nitro, hidroxi, alquilo C1-6, alcoxilo C1-6, haloC1-6alquilo, haloC1-6alcoxilo, hidroxiC1- 6alquilo, hidroxiC1-6alcoxilo, alcoxi C1-6-alquilo C1-6, alcoxi C1-6-alcoxilo C1-6, amino, alquilamino C1-6, bi(alquil C1-6)amino, aminoC1-6alquilo, alquil C1-6-aminoC1-6alquilo, bi(alquil C1-6)aminoC1-6alquilo, cianoC1-6alquilo, alquilsulfonilo C1- 6, alquilsulfonilamino C1-6, alquilsulfonil C1-6-alquilC1-6amino, sulfamoilo, alquilsulfamoilo C1-6, bi(alquil C1-6)sulfamoilo, alcanoilamino C1-6, alcanoil C1-6-alquil C1-6amino, carbamoilo, alquilcarbamoilo C1-6 y bi(alquil C1-6)carbamoilo.
ARP070103775A 2006-08-24 2007-08-24 DERIVADOS DE 4-(3-METILMORFOLIN-4-IL)PIRIMIDINA Y MORFOLIN-4-IL-PIRIMIDINA COMO INHIBIDORES DE MTOR QUINASA Y PI3K, UNA COMPOSICIoN FARMACEUTICA QUE LOS COMPRENDE Y EL USO DE LOS MISMOS EN LA FABRICACION DE MEDICAMENTOS PARA EL TRATAMIENTO DE DIVERSOS TIPOS DE CANCER. AR062526A1 (es)

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GB0616747A GB0616747D0 (en) 2006-08-24 2006-08-24 Novel compounds
US94854407P 2007-07-09 2007-07-09

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EP (1) EP2057140B1 (es)
JP (1) JP5534811B2 (es)
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AR (1) AR062526A1 (es)
AU (1) AU2007287428B2 (es)
CA (1) CA2660758A1 (es)
CL (1) CL2007002446A1 (es)
CO (1) CO6150160A2 (es)
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